Fully automated production of [C]PiB for clinical use on Trasis-AllinOne synthesizer module.

Pittsburgh compound B ([C]PiB) was the first broadly applied radiotracer with specificity for amyloid-β (Aβ) peptide aggregates in the brain and has since been established as the gold standard for positron emission tomography (PET) employed for clinical in vivo imaging of Aβ plaques, used for imaging applications of Alzheimer's disease (AD), related dementia, and other tauopathies. The use of [C]PiB for routine PET studies is dependent on the production capabilities of each radiochemistry laboratory, subsequently a continuous effort is made to develop suitable and sustainable methods on a variety of auto synthesis platforms. Here we report a fully automated, multi-step radio synthesis, purification, and reformulation of [C]PiB for PET imaging using the Trasis AllinOne synthesis unit, a commonly used commercial radiochemistry module.

Two new species of Western Australian Abantiades Herrich-Schffer (Lepidoptera: Hepialidae) and a description of the female of Abantiades paradoxa (Tindale).

Two new species, Abantiades concordia sp. nov. and Abantiades malleus sp.

Two new endemic species of emAbantiades/em Herrich-Schäffer (Lepidoptera: Hepialidae) from Kangaroo Island, Australia.

Abantiades penneshawensis Moore Beaver sp. nov. and Abantiades rubrus Moore Beaver sp.

The complete mitochondrial genome of the brown pansy butterfly, (Aurivillius, 1894), (Insecta: Lepidoptera: Nymphalidae).

The brown pansy, (Aurivillius, 1894) (Lepidoptera: Nymphalidae), is a widespread West African forest butterfly. Genome skimming by Illumina sequencing allowed assembly of a complete 15,233 bp circular mitogenome from consisting of 79.5% AT nucleotides.

Four new tri-forked species of the Australian genus Abantiades Herrich-Schäffer (Lepidoptera: Hepialidae) from the "dark obscura clade".

A distinct group of Abantiades Herrich-Schäffer species is here confirmed as a valid clade that we refer to as the "dark obscura clade" supported by morphological and mtDNA evidence. The clade is the sister group of A. obscura Simonsen of north-western Australia and comprises four new species: Abantiades centralia sp.

Description of two new Australian species of Abantiades Herrich-Schäffer (Lepidoptera: Hepialidae) and females of two further species with notes on their biogeography.

Abantiades cephalocorvus sp. nov. and Abantiades tembyi sp.

Four new species of Splendid Ghost Moths (Lepidoptera: Hepialidae: Aenetus) from Australia and Papua New Guinea.

Four new Aenetus Herrich-Schäffer species are described from northern Australasia; Aenetus simonseni sp. nov. from the top-end of the Northern Territory, Australia, A.

Three new ghost moths of the genus Oxycanus Walker, 1856 from Australia (Lepidoptera: Hepialidae).

Three new species of ghost moth, Oxycanus ephemerous sp. nov., O.

RIPK1 is a critical modulator of both tonic and TLR-responsive inflammatory and cell death pathways in human macrophage differentiation.

In this study, we took advantage of human-induced pluripotent stem cells (hiPSC) and CRISPR/Cas9 technology to investigate the potential roles of RIPK1 in regulating hematopoiesis and macrophage differentiation, proinflammatory activation, and cell death pathways. Knock-out of RIPK1 in hiPSCs demonstrated that this protein is not required for erythro-myeloid differentiation. Using a well-established macrophage differentiation protocol, knock-out of RIPK1 did not block the differentiation of iPSC-derived macrophages, which displayed a similar phenotype to WT hiPSC-derived macrophages.

Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages.

Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs.

The nature and nurture of cell heterogeneity: accounting for macrophage gene-environment interactions with single-cell RNA-Seq.

Background: Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome's limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic 'snapshots' of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic ('nature') and environmental ('nurture') modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages.

MAIT cells are activated during human viral infections.

Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus.

CRISPR-mediated genotypic and phenotypic correction of a chronic granulomatous disease mutation in human iPS cells.

Chronic granulomatous disease (CGD) is a rare genetic disease characterized by severe and persistent childhood infections. It is caused by the lack of an antipathogen oxidative burst, normally performed by phagocytic cells to contain and clear bacterial and fungal growth. Restoration of immune function can be achieved with heterologous bone marrow transplantation; however, autologous bone marrow transplantation would be a preferable option.

Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection.

Intramolecular oxonium ylide formation-[2,3] sigmatropic rearrangement of diazocarbonyl-substituted cyclic unsaturated acetals: a formal synthesis of hyperolactone C.

Rh(II)-catalyzed oxonium ylide formation-[2,3] sigmatropic rearrangement of α-diazo-β-ketoesters possessing γ-cyclic unsaturated acetal substitution, followed by acid-catalyzed elimination-lactonization, provides a concise approach to 1,7-dioxaspiro[4.4]non-2-ene-4,6-diones. The process creates adjacent quaternary stereocenters with full control of the relative stereochemistry.

The productive entry pathway of HIV-1 in macrophages is dependent on endocytosis through lipid rafts containing CD4.

Macrophages constitute an important reservoir of HIV-1 infection, yet HIV-1 entry into these cells is poorly understood due to the difficulty in genetically manipulating primary macrophages. We developed an effective genetic approach to manipulate the sub-cellular distribution of CD4 in macrophages, and investigated how this affects the HIV-1 entry pathway. Pluripotent Stem Cells (PSC) were transduced with lentiviral vectors designed to manipulate CD4 location and were then differentiated into genetically modified macrophages.

Informatics calibration of a molecular descriptors database to predict solid dispersion potential of small molecule organic solids.

The use of a novel, in silico method for making an intelligent polymer selection to physically stabilize small molecule organic (SMO) solid compounds formulated as amorphous molecular solid dispersions is reported. 12 compounds (75%, w/w) were individually co-solidified with polyvinyl pyrrolidone:vinyl acetate (PVPva) copolymer by melt-quenching. Co-solidified products were analyzed intact using differential scanning calorimetry (DSC) and the pair distribution function (PDF) transform of powder X-ray diffraction (PXRD) data to assess miscibility.

Multiple barriers to recombination between divergent HIV-1 variants revealed by a dual-marker recombination assay.

Recombination is a major force for generating human immunodeficiency virus type 1 (HIV-1) diversity and produces numerous recombinants circulating in the human population. We previously established a cell-based system using green fluorescent protein gene (gfp) as a reporter to study the mechanisms of HIV-1 recombination. We now report an improved system capable of detecting recombination using authentic viral sequences.

Protection of HIV neutralizing aptamers against rectal and vaginal nucleases: implications for RNA-based therapeutics.

RNA-based drugs are an emerging class of therapeutics. They have the potential to regulate proteins, chromatin, as well as bind to specific proteins of interest in the form of aptamers. These aptamers are protected from nuclease attack by chemical modifications that enhance their stability for in vivo usage.

Structural interpretation in composite systems using powder X-ray diffraction: applications of error propagation to the pair distribution function.

Purpose: To develop a method for drawing statistical inferences from differences between multiple experimental pair distribution function (PDF) transforms of powder X-ray diffraction (PXRD) data.

Methods: The appropriate treatment of initial PXRD error estimates using traditional error propagation algorithms was tested using Monte Carlo simulations on amorphous ketoconazole. An amorphous felodipine:polyvinyl pyrrolidone:vinyl acetate (PVPva) physical mixture was prepared to define an error threshold.

Delineation of the preferences and requirements of the human immunodeficiency virus type 1 dimerization initiation signal by using an in vivo cell-based selection approach.

HIV-1 packages two copies of RNA into one particle, and the dimerization initiation signal (DIS) in the viral RNA plays an important role in selecting the copackaged RNA partner. We analyzed the DIS sequences of the circulating HIV-1 isolates in the GenBank database and observed that, in addition to the prevalent GCGCGC, GTGCAC, and GTGCGC sequences, there are many other minor variants. To better understand the requirements for the DIS to carry out its function, we generated a plasmid library containing a subtype B HIV-1 genome with a randomized DIS, infected cells with viruses derived from the library, and monitored the emergence of variants at different time points until 100 days postinfection.

Probing the HIV-1 genomic RNA trafficking pathway and dimerization by genetic recombination and single virion analyses.

Once transcribed, the nascent full-length RNA of HIV-1 must travel to the appropriate host cell sites to be translated or to find a partner RNA for copackaging to form newly generated viruses. In this report, we sought to delineate the location where HIV-1 RNA initiates dimerization and the influence of the RNA transport pathway used by the virus on downstream events essential to viral replication. Using a cell-fusion-dependent recombination assay, we demonstrate that the two RNAs destined for copackaging into the same virion select each other mostly within the cytoplasm.

A structural investigation into the compaction behavior of pharmaceutical composites using powder X-ray diffraction and total scattering analysis.

Purpose: To use advanced powder X-ray diffraction (PXRD) to characterize the structure of anhydrous theophylline following compaction, alone, and as part of a binary mixture with either alpha-lactose monohydrate or microcrystalline cellulose.

Materials And Methods: Compacts formed from (1) pure theophylline and (2) each type of binary mixture were analyzed intact using PXRD. A novel mathematical technique was used to accurately separate multi-component diffraction patterns.

HIV-1 RNA dimerization: It takes two to tango.

Each viral particle of HIV-1, the infectious agent of AIDS, contains two copies of the full-length viral genomic RNA. Encapsidating two copies of genomic RNA is one of the characteristics of the retrovirus family. The two RNA molecules are both positive-sense and often identical; furthermore, each RNA encodes the full complement of genetic information required for viral replication.